Precise excitation-inhibition balance controls gain and timing in the hippocampus
- Tata Institute of Fundamental Research, India
Abstract
Excitation-inhibition (EI) balance controls excitability, dynamic range, and input gating in many brain circuits. Subsets of synaptic input can be selected or 'gated' by precise modulation of finely tuned EI balance, but assessing the granularity of EI balance requires combinatorial analysis of excitatory and inhibitory inputs. Using patterned optogenetic stimulation of mouse hippocampal CA3 neurons, we show that hundreds of unique CA3 input combinations recruit excitation and inhibition with a nearly identical ratio, demonstrating precise EI balance at the hippocampus. Crucially, the delay between excitation and inhibition decreases as excitatory input increases from a few synapses to tens of synapses. This creates a dynamic millisecond-range window for postsynaptic excitation, controlling membrane depolarization amplitude and timing via subthreshold divisive normalization. We suggest that this combination of precise EI balance and dynamic EI delays forms a general mechanism for millisecond-range input gating and subthreshold gain control in feedforward networks.
Data availability
All simulation data and code are open source and online, available at https://github.com/sahilm89/linearity. Experimental data is available on Dryad (DOI: https://doi.org/10.5061/dryad.f456k4f) .
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Data from: Precise excitation-inhibition balance controls gain and timing in the hippocampusDryad Digital Repository, doi.org/10.5061/dryad.f456k4f.
Article and author information
Author details
Upinder Singh Bhalla
Funding
University Grants Commission (UGC/ISF No. F 6-18/2014 (IC))
- Upinder Singh Bhalla
Israel Science Foundation (UGC/ISF No. F 6-18/2014 (IC))
- Upinder Singh Bhalla
Council of Scientific and Industrial Research (Senior Research Fellowship)
- Sahil Moza
National Centre for Biological Sciences (Graduate Student Fellowship)
- Aanchal Bhatia
- Sahil Moza
- Upinder Singh Bhalla
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures were approved by the National Centre for Biological Sciences Institutional Animal Ethics Committee (Protocol number USB-19-1/2011), in accordance with the guidelines of the Government of India (animal facility CPCSEA registration number 109/1999/CPCSEA) and equivalent guidelines of the Society for Neuroscience. CA3-cre (C57BL/6-Tg (Grik4-cre) G32-4Stl/J mice, Stock number 006474) were obtained from Jackson Laboratories. The animals were housed in a temperature controlled environment with a 14-h light: 10h dark cycle, with ad libitum food and water.
Copyright
© 2019, Bhatia et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Precise excitation-inhibition balance controls gain and timing in the hippocampus
eLife 8:e43415.
https://doi.org/10.7554/eLife.43415
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